HIF-1α/STAT3信号介导小胶质细胞不同极化在缺血性脑卒中的机制研究

The polarization of neuro-protective effects of M2 microglia (M2-MG) toward an inflammatory M1 microglia (M1-MG) can elicit inflammatory cascade and aggravate inflammation damage after ischemic brain injury. However, its mechanism is not clear. Our results suggested that the HIF-1α/STAT3 signal pathway played an important role in the M2-MG polarization to M1-MG process. Therefore, we proposed that HIF-1α/STAT3 signal might contribute to M2-MG polarization to M1-MG by regulating the expression of Notch1. To explore the mechanism of M2-MG polarization to M1-MG, M2-MG was respectively transfected with HIF1a-siRNA and STAT3-siRNA. To analysis HIF1a/STAT3/Notch1 signal effects on the polarization of microglia, inflammatory cascade damage and neuroprotection, cerebrospinal fluid were injected recombinant lentivirus loading HIF1a-siRNA and STAT3-siRNA in the animal level. This research will provide theoretical and experimental basis for treatment of ischemic brain injury.

缺血性脑卒中后，M2型小胶质细胞（M2 microglia, M2-MG）向M1型小胶质细胞（M1 microglia,M1-MG）极化，是启动炎症级联反应并加剧神经损伤的重要原因，但其机制不清。我们的预实验提示HIF-1α/STAT3是调控M2-MG极化为M1-MG的关键信号。为此，我们提出HIF-1α/STAT3信号可能通过调控下游Notch1分子的表达促进M2-MG极化为M1-MG。本项目拟使用HIF1α-siRNA、STAT3-siRNA分别抑制M2-MG的HIF1a和STAT3的表达，从分子、细胞、组织和动物水平探讨在急性缺氧条件下HIF1a/STAT3/Notch1信号调控M2-MG极化为M1-MG的机制，分析其对炎症级联损伤和神经功能改善的影响，为缺血性脑损伤的治疗提供理论和实验基础。

缺血性脑卒中后，M2型小胶质细胞（M2 microglia,M2-MG）向M1型小胶质细胞（M1-MG）极化，是启动炎症级联反应并加剧神经损伤的重要原因。本实验证实HIF-1α/STAT3是调控M2-MG极化为M1-MG的关键信号。保护濒死神经元是缺血性脑损伤的主要措施，氧化应激和炎症级联反应是缺血性脑卒中神经元凋亡的重要原因。本实验制备能够清除氧自由基和抑制炎症级联反应的双功能纳米药物，改善缺血半暗带微环境、保护濒死神经元，为缺血性脑损伤奠定理论基础和提供有效的治疗方法。